Localized amyloidosis of the stomach mimicking a superficial gastric cancer

A 73-year-old man was referred to our hospital for further examination of a depressed lesion in the stomach found by cancer screening gastroscopy. A barium upper gastrointestinal series showed an area of irregular mucosa measuring 15 mm on the anterior wall of the gastric body. Esophagogastroduodenoscopy revealed a 15 mm depressed lesion on the anterior wall of the lower gastric body. We suspected an undifferentiated adenocarcinoma from the appearance and took some biopsies. However, histology of the specimens revealed amyloidal deposits in the submucosal layer without malignant findings. Congo red staining was positive for amyloidal protein and green birefringence was observed under polarized light microscopy. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid type. There were no amyloid deposits in the colon or duodenum. Computed tomography of the chest, abdomen, and pelvis showed no remarkable findings. Thus, this case was diagnosed as a localized gastric amyloidosis characterized by AL type amyloid deposition in the mucosal or submucosal layer. As the clinical outcome of gastric AL amyloidosis seems favorable, this case is scheduled for periodic examination to recognize potential disease progression and has been stable for 2 years.     

A rare etiology of mild encephalitis/encephalopathy with reversible splenial lesion

Legionella is a rare cause of mild encephalitis/encephalopathy with reversible splenial lesion, which should be considered in patients with risk factors. Brain magnetic resonance imaging (MRI) and legionella urinary antigen test can help the diagnosis since cerebrospinal fluid (CSF) can be normal.     

Long-term survival estimates in older patients with pathological stage I gastric cancer undergoing gastrectomy: Duocentric analysis of simplified scoring system

BackgroundOur aim was to determine factors predictive of long-term post-gastrectomy outcomes in older adults with pathological stage I gastric cancer (GC).MethodsA total of 175 patients with resected pathological stage I GC at two institutions were reviewed, each ≥75 years old at the time of gastrectomy and full participants in a 5-year follow-up program. The procedures were undertaken between January 2006 and December 2011. Patients were divided into two groups: survivors and non-survivors at postoperative Year 5. Univariate and multivariate analyses were applied to identify independent predictors of 5-years survival, including preoperative, surgical, and histopathologic variables.ResultsMultivariate analysis of overall survival (OS) at 5 years indicated that prognostic nutritional index (PNI) <45 and the American Society of Anesthesiologists physical status (ASA-PS) 3 were independently associated with unfavorable outcomes. A clinical score consisting of 1-point each for these two variables proved useful in predicting survival after gastrectomy (5-year OS: 0 point, 86.6%; 1-point, 51.6%; 2-point, 33.3%; p < .001, area under the curve [AUC] = 0.757).ConclusionsLong-term survival of older adults with pathological stage I GC is unfavorable in patients displaying both ASA-PS 3 and PNI < 45. A simple scoring method, based on combined ASA-PS/PNI determinations, provides an accurate prognostic prediction for these patients.     

Mutation analysis of Rad18 in human cancer cell lines and non small cell lung cancer tissues

Background

Genetic instability is known as a cause of oncogenesis. Though Rad18 is reported to function in a post replication mismatch repair system, the relation between the status of Rad18 and human tumorigenesis has not been described so far.

Methods

Mutation analysis of 34 human cancer cell lines and 32 non small cell lung cancer (NSCLC) tissues were performed by RT-PCR SSCP. Expression level of Rad18 was measured by real time RT-PCR. Stable transfectant was constructed for in vitro study.

Results

No mutation was found in both cancer cell lines and NSCLC tissues. A single nucleotide polymorphism (SNP) at codon 302 was detected in 51.5% of the cell lines and 62.5% of NSCLC tissues. Interestingly, Rad18 was homozygously deleted in a pulmonary adenocarcinoma cell line PC3. Furthermore, there was no difference in the expression level of wild type Rad18 and Rad18 with SNP. The growth, cell morphology, sensitivity to anti-cancer drugs and in vitro DNA repair activity between wild type Rad18 and Rad18 with SNP revealed to have no difference in vitro.

Conclusion

Though the frequency of SNP was tended to be higher in NSCLC patients than healthy volunteers (57.7%), as the difference was not significant, we have concluded that there is no relation between Rad18 SNP and lung cancer development.     

Biochemical and histopathological studies on a mouse brain ischemic model induced by bilateral carotid artery occlusion: comparison with the carbon monoxide inhalation method and other ischemic or anoxic models

Bilateral occlusion of the carotid arteries (BCAO) killed 52% of the male ddY mice (N = 86) and 77% of the ICR mice (N = 96) within 10 min, and the mean survival time of the ddY strain recorded for the 10 min was significantly longer than the time of the ICR strain. Among animals that survived longer than 1 hr after BCAO, some (5 of ddY and 3 of ICR) were able to survive for more than 24 hr. All of the neurobehavioral and histopathological signs developed by BCAO and in most cases followed by death were found to be also inducible by unilateral occlusion alone, although this was in a small fraction of mice. The brain levels of ATP, glucose and acetylcholine significantly decreased in mice that died within 10 min after BCAO, while none of these changes were detectable in mice surviving BCAO for 1 hr, just as in mice that died by carbon monoxide or ether inhalation. The results obtained herein indicate that mice may not be homogeneous in the functional level of the collateral route of blood supply to the brain tissue and/or in the sensitivity toward the ischemia-inducible lethality.     

Carbon monoxide (CO)-induced hypoxia in mice: evaluation as an experimental model of cerebral ischemia for drug screening

An injection of 12.5 ml of carbon monoxide (CO) gas into an air-filled chamber (780 ml in volume) caused the death of the ICR or ddY mouse (6-8 weeks old) inside. The average survival time was 2.5 min for either sex of animals treated with nothing or saline and never exceeded 8 min. Pretreatment with pentobarbital Na (30 mg/kg, i.p.), hopantenate Ca (100 mg/kg, i.p.), vinpocetine (5 mg/kg, i.p. or 50 mg/kg, p.o.), flunarizine HCl (5 mg/kg, i.p.), glucose (6 g/kg, i.p.), phenobarbital (30 mg/kg, i.p.), phenytoin (20 mg/kg, i.p.), arginine HCl (100 mg/kg, i.p. or 1 g/kg, p.o.) and alanine (100 mg/kg, i.p. or 1 g/kg, p.o.) prolonged the survival time of male mice. Insofar as tested, female mice responded rather poorly to these pretreatments. Survival for longer than 8 min occurred in some of the drug-pretreated animals of either sex. To be noted is the finding that most of the animals which survived 8 min once were able to survive the second 8 min on the following day without any drug-treatment. Monitoring of the time course of carboxyhemoglobin formation revealed that the carboxyhemoglobin level reached a plateau of 70% saturation within 2 min and then gradually increased. The lethal level was about 72%. Pentobarbital decreased the formation rate but did not elevate the lethal level. The results indicate that the CO-induced hypoxia model of mice is usable for screening of drug candidates which may be effective for treatment of human ischemic diseases.     

Evaluation of the vasodilating effect of naftidrofuryl oxalate using isolated canine and rat artery preparations

Using isolated ring preparations of major arteries mainly of canine origin, we attempted to explore the mechanism of the vasodilating effect of naftidrofuryl oxalate (I) at the concentration of approximately 10 microM. 1) The resting tension of canine carotid, femoral, coronary, renal and basilar arteries were not affected by I. 2) A weak or no papaverine-like activity was noted on coronary, renal and basilar arteries contracted by KCl (25 mM) or U46619 (20 nM). Porcine endothelin (30 nM)-induced contraction in the basilar artery also showed no response to I. 3) I produced a relatively strong anti-serotonergic effect in the basilar and femoral arteries, and the minimum effective concentrations of I for pretreating these arteries were 0.3 and 0.1 microM, respectively. I failed, however, to affect 8-OH-DPAT-induced contraction of the basilar artery. 4) In a low concentration such as 1 nM, I was able to release the vasodilating factor from the carotid artery. 5) The oscillatory contractions which developed in the rat thoracic aorta with phenylephrine (10 microM) were not affected by I (approximately 0.1 microM). 6) Na oxalate (approximately 1 mM) produced none of the effects of I described in 2) approximately 4). Based on the results obtained, it is concluded that I would exert its vasodilating effect not only directly via an anti-serotonergic action but also indirectly via its secretagogue-like action.     

Suppression of proliferation of poliovirus and porcine parvovirus by novel phenoxazines, 2-amino-4,4 alpha-dihydro-4 alpha-7-dimethyl-3H-phenoxazine-3-one and 3-amino-1,4 alpha-dihydro-4 alpha-8-dimethyl-2H-phenoxazine-2-one

The present study aimed at investigating the antiviral effects of 2-amino-4,4alpha-dihydro-4alpha-7-dimethyl-3H-phenoxazine-3-one (Phx-1) and 3-amino-1,4alpha-dihydro-4alpha-8-dimethyl-2H-phenoxazine-2-one (Phx-2) on 6 representative viruses: poliovirus, porcine parvovirus, simian virus 40 (SV-40), herpes simplex virus-1 (HSV-1), Sindbis virus, and vesicular stomatitis virus (VSV). Phx-1 and Phx-2 suppressed the proliferation of poliovirus in Vero cells and that of porcine parvovirus in ESK cells at concentrations between 0.25 microg/ml and 2 microg/ml, when the cells were treated with Phx-1 and Phx-2 for 1 h and then inoculated with these viruses. The proliferation of the other viruses, SV-40, HSV-1, Sindbis virus, and VSV, in the host cells was not influenced by Phx-1 or Phx-2 at concentrations less than 20 microg/ml. The results suggest that Phx-1 and Phx-2 may be useful to prevent the proliferation of poliovirus and porcine parvovirus infection and may contribute to developing new antiviral drugs in future.     

Sinus histiocytosis with massive lymphadenopathy in a Japanese adult with unusually elevated EBV antibody titers

A 35-year-old Japanese male was presented with massive lymphadenopathy in bilateral preauricular and submandibular regions for five years' duration without any complaints despite of no specific treatments. Laboratory examinations revealed neurtrophilia, elevated BSR, hypergammaglobulinemia with elevated IgG and IgM, positive CRP and RA, low percentage of T-cells in peripheral blood, impaired PHA blast transformation, and elevated EBV titers against viral capsid, early and nuclear antigens. Biopsy specimens demonstrated massive histiocytosis with hemophagocytosis in the sinuses and predominant mature plasma cells in the medulla, which were fairly well consistent with "sinus histiocytosis with massive lymphadenopathy" (ROSAI and DORFMAN). Ultrastructural study revealed histiocytes exhibiting avid phagocytosis of blood cells, epithelioid histiocytes with poor phagocytic activity, foamy storage histiocytes loaded with a large number of osmiophilic lipid granules and giant cells of various types. Pathogenesis of this apparently benign disease entity was briefly discussed, and its refractoriness against any specific therapy was emphasized.     

Attenuating effect of artemin on herpes-related pain responses in mice infected with herpes simplex

The influence of artemin (AR) on herpes-related pain responses was examined using mice infected with herpes simplex virus (HSV). BALB/c mice were inoculated with HSV (1x10(6) plaque-forming units) on the right hind paw, while the contralateral hind paw was without inoculation. The changes in nociceptive threshold were examined using an electric Von Fray meter. Intraperitoneal administration of AR prevented a decrease in nociceptive threshold dose-dependently in HSV-inoculated mice, which was first observed at a dose of 1.0 mg/kg and peaked at doses higher than 1.5 mg/kg. This antinociceptive effect of AR attained peaks at 120 min after administration and declined gradually to non-treated levels by 270 min. Intraperitoneal administration of AR at a dose of 1.5 mg/kg scarcely affected beta-endorphin and noradrenaline levels in the central nervous system of HSV-inoculated mice. However, AR caused a significant decrease of the dynorphin levels in spinal cord. These results strongly suggest that AR exerts antinociceptive effects on herpes-related pain through changes of the dynorphin levels in the central nervous system of HSV-inoculated mice. It is also suggested that AR will be a good candidate as an antinociceptive drug for the treatment of acute herpetic pain in humans.